Sex hormones modulation of spontaneous autoimmune disease in NZB/NZW F1 mice (B/W) has been studied in four main areas: 1) Ability of 5-alpha dihydrotestosterone to suppress autoimmune disease in older animals. The results present no significant decrease of antiDNA antibodies; therefore androgen can still prolong survival in spite of the disease already well established. 2) Evaluation of Domazol, a weakly androgenic synthetic compound, as possible androgen substitution: no therapeutic effects are obtained. 3) Use of "in-vitro" spleen cell system for spontaneous autoantibodies production shows that autoimmune animals produce more antibodies to dsDNA than normal controls; autoantibody production in B/W mice is T cell and accessory cell dependent. 4) Comparison of thymosin fraction V and 5-alpha dihydrotestosterone shows no beneficial effect on thymos in V-treated mice. Androgen-treated mice survived longer, and their spleen cells had an increase in PHA mitogenic response, suggesting that androgen might influence a mature peripheral T cell.